Nanoscale ATP-Responsive Zeolitic Imidazole Framework-90 as a General Platform for Cytosolic Protein Delivery and Genome Editing

J Am Chem Soc. 2019 Mar 6;141(9):3782-3786. doi: 10.1021/jacs.8b11996. Epub 2019 Feb 8.

Abstract

Metal-organic frameworks (MOFs) are an emerging class of nanocarriers for drug delivery, owing to their tunable chemical functionality. Here we report ATP-responsive zeolitic imidazole framework-90 (ZIF-90) as a general platform for cytosolic protein delivery and CRISPR/Cas9 genome editing. The self-assembly of imidazole-2-carboxaldehyde and Zn2+ with protein forms ZIF-90/protein nanoparticles and efficiently encapsulates protein. It was found that, in the presence of ATP, the ZIF-90/protein nanoparticles are degraded to release protein due to the competitive coordination between ATP and the Zn2+ of ZIF-90. Intracellular delivery studies showed that the ZIF-90/protein nanoparticle can deliver a large variety of proteins into the cytosol, regardless of protein size and molecular weight. The delivery of cytotoxic RNase A efficiently prohibits tumor cell growth, while the effective delivery of genome-editing protein Cas9 knocks out the green fluorescent protein (GFP) expression of HeLa cells with efficiency up to 35%. Given the fact that ATP is upregulated in disease cells, it is envisaged that the ATP-responsive protein delivery will open up new opportunities for an advanced protein delivery and CRISPR/Cas9 genome editing for targeted disease treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / chemistry*
  • Carrier Proteins* / chemistry
  • Carrier Proteins* / genetics
  • Cytosol / chemistry*
  • Gene Editing
  • HeLa Cells
  • Humans
  • Imidazoles / chemistry*
  • Nanoparticles / chemistry*
  • Zeolites / chemistry*

Substances

  • Carrier Proteins
  • Imidazoles
  • Zeolites
  • imidazole
  • Adenosine Triphosphate